Isopropanol → 3-Amino-6-fluorobenzo[b]thiophene-2-carboxylic acid

HRID 501296Notes

Reaction equation

HRID 501296 reaction equation
[C:1]([C:5]1[S:9][C:8]2[CH:10]=[C:11]([F:14])[CH:12]=[CH:13][C:7]=2[C:6]=1[NH2:15])([O:3]C)=[O:2].[OH-].[Na+].C(O)(C)C>O>[NH2:15][C:6]1[C:7]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:8]=2[S:9][C:5]=1[C:1]([OH:3])=[O:2]

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 14798Sodium HydroxideHCID 10585280Methyl 3-amino-6-fluoro-1-benzothiophene-2-carboxylate

Product 1

HCID 231124713-Amino-6-fluorobenzo[b]thiophene-2-carboxylic acidYield 94.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
8.5 °C

Procedure

At 50° C., add to a stirring solution of 2-carbomethoxy-3-amino-6-fluoro-benzo[b]thiophene (prepared according to U.S. Pat. No. 5,143,923), (90.1 g, 0.4 mol) in H2O (450 mL), a 50% aqueous solution of NaOH (64 g, 0.8 mol) over 2-3 min. Heat the reaction to 70-73° C. and continue to stir for 3 h. Add 10% aqueous isopropanol (45 mL) and bring to reflux. Remove the isopropanol under N2 and add H2O (300 mL). Cool the reaction mixture to between 7-10° C. and add concentrated HCl (80 mL). Add H2O (650 mL), cool to 5-70° C., filter the resulting solid, and wash the filter cake with H2O (2×150 mL). Dry the solid under vacuum at 35° C. to obtain 80.6 g (94.7%) of solid mp 160-163° C., TLC on silica gel (dichloromethane/methanol, 3:1), Rf=0.69.

Workup

  1. customprepared
  2. temperatureHeat
  3. customthe reaction to 70-73° C.
  4. temperatureto reflux
  5. customRemove the isopropanol under N2
  6. additionadd H2O (300 mL)
  7. additionadd concentrated HCl (80 mL)
  8. temperatureAdd H2O (650 mL), cool to 5-70° C.
  9. filtrationfilter the resulting solid
  10. washwash the filter cake with H2O (2×150 mL)
  11. customDry the solid under vacuum at 35° C.

Sources & evidence

ORD record
ord-6efc30f72f9841bf8eb79bb7b61a8798
Source dataset
uspto-grants-2010_08
Patent number
US07772252B2

Reaction notes

Loading…